MDM1 is a microtubule-binding protein that negatively regulates centriole duplication

Molecular Biology of the Cell
Daniel Van de MarkTim Stearns

Abstract

Mouse double-minute 1 (Mdm1) was originally identified as a gene amplified in transformed mouse cells and more recently as being highly up-regulated during differentiation of multiciliated epithelial cells, a specialized cell type having hundreds of centrioles and motile cilia. Here we show that the MDM1 protein localizes to centrioles of dividing cells and differentiating multiciliated cells. 3D-SIM microscopy showed that MDM1 is closely associated with the centriole barrel, likely residing in the centriole lumen. Overexpression of MDM1 suppressed centriole duplication, whereas depletion of MDM1 resulted in an increase in granular material that likely represents early intermediates in centriole formation. We show that MDM1 binds microtubules in vivo and in vitro. We identified a repeat motif in MDM1 that is required for efficient microtubule binding and found that these repeats are also present in CCSAP, another microtubule-binding protein. We propose that MDM1 is a negative regulator of centriole duplication and that its function is mediated through microtubule binding.

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Citations

Sep 23, 2016·PloS One·Monica R HensleyGuangJun Zhang
Mar 30, 2018·Nature Communications·Gaëlle MarteilMónica Bettencourt-Dias
May 8, 2018·IUBMB Life·Anuradha Kumari, Dulal Panda
Jan 13, 2017·Journal of Molecular Cell Biology·Ban Xiong TanCynthia R Coffill

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Methods Mentioned

BETA
transfection
confocal microscopy
flow cytometry
electron microscopy
fluorescence microscopy
transmission electron microscopy
PCR
transfections
light microscopy
fluorescence imaging

Software Mentioned

CLEM
BLAST
SoftWoRx
Fiji
Interactive Tree of Life
Clustal Omega
Photoshop
RStudio
ImageJ
Excel

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